The Resorcinarene Hexameric Capsule as a Supramolecular Photoacid to Trigger Olefin Hydroarylation in Confined Space.

The self-assembled resorcinarene capsule C6 shows remarkable photoacidity upon light irradiation, which is here exploited to catalyze olefin hydroarylation reactions in confined space. An experimental pKa* value range of -3.3--2.8 was estimated for the photo-excited hexameric capsule C6*, and consequently an increase in acidity of 8.8 log units was observed with respect to its ground state (pKa=5.5-6.0). This makes the hexameric capsule the first example of a self-assembled supramolecular photoacid. The photoacid C6* can catalyze hydroarylation reaction of olefins with aromatic substrates inside its cavity, while no reaction occurred between them in the absence of irradiation and/or capsule. DFT calculations corroborated a mechanism in which the photoacidity of C6* plays a crucial role in the protonation step of the aromatic substrate. A further proton transfer to olefin with a concomitant C-C bond formation and a final deprotonation step lead to product releasing.

The mechanism of visible light-induced C-C cross-coupling by Csp3-H bond activation.

Csp3-C cross-coupling by activating Csp3-H bonds is a dream reaction for the chemical community, and visible light-induced transition metal-catalysis under mild reaction conditions is considered a powerful tool to achieve it. Advancement of this research area is still in its infancy because of the chemical and technical complexity of this catalysis. Mechanistic studies illuminating the operative reaction pathways can rationalize the increasing amount of experimental catalysis data and provide the knowledge allowing faster and rational advances in the field. This goal requires complementary experimental and theoretical mechanistic studies, as each of them is unfit to clarify the operative mechanisms alone. In this tutorial review we summarize representative experimental and computational mechanistic studies, highlighting weaknesses, strengths, and synergies between the two approaches.

Photoexcitation of Distinct Divalent Palladium Complexes in Cross-Coupling Amination Under Air.

The development of metal complexes that function as both photocatalyst and cross-coupling catalyst remains a challenging research topic. So far, progress has been shown in palladium(0) excited-state transition metal catalysis for the construction of carbon-carbon bonds where the oxidative addition of alkyl/aryl halides to zero-valent palladium (Pd0 ) is achievable at room temperature. In contrast, the analogous process with divalent palladium (PdII ) is uphill and endothermic. For the first time, we report that divalent palladium can act as a light-absorbing species that undergoes double excitation to realize carbon-nitrogen (C-N) cross-couplings under air. Differently substituted aryl halides can be applied in the mild, and selective cross-coupling amination using palladium acetate as both photocatalyst and cross-coupling catalyst at room temperature. Density functional theory studies supported by mechanistic investigations provide insight into the reaction mechanism.

Nickel-Mediated Enantioselective Photoredox Allylation of Aldehydes with Visible Light.

Here we report a practical, highly enantioselective photoredox allylation of aldehydes mediated by chiral nickel complexes with commercially available allyl acetate as the allylating agent. The methodology allows the clean stereoselective allylation of aldehydes in good to excellent yields and up to 93 % e.e. using a catalytic amount of NiCl2 (glyme) in the presence of the chiral aminoindanol-derived bis(oxazoline) as the chiral ligand. The photoredox system is constituted by the organic dye 3DPAFIPN and a Hantzsch's ester as the sacrificial reductant. The reaction proceeds under visible-light irradiation (blue LEDs, 456 nm) at 8-12 °C. Compared to other published procedures, no metal reductants (such as Zn or Mn), additives (e.g. CuI) or air-sensitive Ni(COD)2 are necessary for this reaction. Accurate DFT calculations and photophysical experiments have clarified the mechanistic picture of this stereoselective allylation reaction.

Adsorptive Molecular Sieving of Styrene over Ethylbenzene by Trianglimine Crystals.

The separation of styrene (ST) and ethylbenzene (EB) mixtures is of great importance in the petrochemical and plastics industries. Current technology employs multiple cycles of energy-intensive distillation due to the very close boiling points of ST and EB. Here, we show that the molecular sieving properties of easily scalable and stable trianglimine crystals offer ultrahigh selectivity (99%) for styrene separation. The unique molecular sieving properties of trianglimine crystals are corroborated by DFT calculations, suggesting that the incorporation of the nonplanar EB requires a significant deformation of the macrocyclic cavity whereas the planar ST can be easily accommodated in the cavity.

Regiodivergent Hydroborative Ring Opening of Epoxides via Selective C-O Bond Activation.

A magnesium-catalyzed regiodivergent C-O bond cleavage protocol is presented. Readily available magnesium catalysts achieve the selective hydroboration of a wide range of epoxides and oxetanes yielding secondary and tertiary alcohols in excellent yields and regioselectivities. Experimental mechanistic investigations and DFT calculations provide insight into the unexpected regiodivergence and explain the different mechanisms of the C-O bond activation and product formation.

Mechanistic Insight into the Photoredox-Nickel-HAT Triple Catalyzed Arylation and Alkylation of α-Amino Csp3-H Bonds.

We report here a comprehensive computational analysis of the mechanisms of the photoredox-nickel-HAT (HAT: hydrogen atom transfer) catalyzed arylation and alkylation of α-amino Csp3-H bonds developed by MacMillan and co-workers. Different alternatives for the three catalytic cycles were tested to identify unambiguously the operative reaction mechanism. Our analysis indicated that the IrIII photoredox catalyst, upon irradiation with visible light, can be either reduced or oxidized by the HAT and nickel catalysts, respectively, indicating that both reductive and oxidative quenching catalytic cycles can be operative, although the reductive cycle is favored. Our analysis of the HAT cycle indicated that activation of a α-amino Csp3-H bond of the substrate is facile and selective relative to activation of a ß-amino Csp3-H bond. Finally, our analysis of the nickel cycle indicated that both arylation and alkylation of α-amino Csp3-H bonds occurs via the sequence of nickel oxidation states NiI-NiII-NiI-NiIII and of elementary steps: radical addition-SET-oxidative addition-reductive elimination.

Asymmetric Hydroboration of Heteroaryl Ketones by Aluminum Catalysis.

A series of methyl aluminum complexes bearing chiral biphenol-type ligands were found to be highly active catalysts in the asymmetric reduction of heterocyclic ketones (S/C = 100-500, ee up to 99%). The protocol is suitable for a wide range of substrates and has a high tolerance to functional groups. The formed 2-heterocyclic-alcohols are valuable building blocks in drug discovery or can be used as ligands in asymmetric catalysis. Isolation and comprehensive characterization of the reaction intermediates support a catalysis cycle proposed by DFT calculations.

Unprecedented Diastereoselective Arylogous Michael Addition of Unactivated Phthalides.

The first highly enantioselective arylogous Michael reaction (AMR) of 3-unsubstituted phthalides has been described. This phase-transfer methodology, which uses catalytic amounts of KOH/18-crown-6 catalyst in mesitylene in the presence of N,O-bis(trimethylsilyl)acetamide (BSA), gives access to a broad range of 3-monosubstituted phthalides with high levels of syn diastereoselectivity and good yields, starting from 3-unsubstituted derivatives and diverse α,ß-unsaturated carbonyl compounds. The reaction also applies to unactivated 3-alkyl phthalides to afford 3,3-dialkyl derivatives. A plausible mechanism has been suggested. DFT analysis of possible transition states gives a rationale of the high syn diastereoselectivity observed and its correlation with the solvent's dielectric constant.

Evaluation of experimental alkali metal ion-ligand noncovalent bond strengths with DLPNO-CCSD(T) method.

We applied the domain based local pair natural orbital coupled cluster approach with single, double, and perturbative triple excitations, DLPNO-CCSD(T), to rationalize more than 130 experimental bond dissociation enthalpies collected in the work of Rodgers and Armentrout [Chem. Rev. 116, 5642-5687 (2016)] and involving alkali metal cations and versatile neutral organic and inorganic ligands ranging from common solvents to amino acids. In general, a remarkable agreement has been obtained between predicted and experimental alkali metal ion-ligand noncovalent bond strengths, highlighting a high degree of reliability of data assembled by Rodgers and Armentrout. In the case of some inconsistent experimental data given for some species, we pointed to a number for which best agreement with DLPNO-CCSD(T) calculations has been achieved. In addition, we refined a couple of ΔH0 for which DLPNO-CCSD(T) values turned out to be significantly different from their experimental counterparts. We suggest an application of the DLPNO-CCSD(T) to derive the reference values to train/validate force field and neural network methods to be further applied in molecular dynamic simulations to unravel the mechanisms in biological systems and alkali metal ion batteries.

Asymmetric Magnesium-Catalyzed Hydroboration by Metal-Ligand Cooperative Catalysis.

Asymmetric catalysis with readily available, cheap, and non-toxic alkaline earth metal catalysts represents a sustainable alternative to conventional synthesis methodologies. In this context, we describe the development of a first MgII -catalyzed enantioselective hydroboration providing the products with excellent yields and enantioselectivities. NMR spectroscopy studies and DFT calculations provide insights into the reaction mechanism and the origin of the enantioselectivity which can be explained by a metal-ligand cooperative catalysis pathway involving a non-innocent ligand.

Magnesium-Catalyzed Hydroboration of Terminal and Internal Alkynes.

A magnesium-catalyzed hydroboration of alkynes providing good yields and selectivities for a wide range of terminal and symmetrical and unsymmetrical internal alkynes has been developed. The compatibility with many functional groups makes this magnesium catalyzed procedure attractive for late stage functionalization. Experimental mechanistic investigations and DFT calculations reveal insights into the reaction mechanism of the magnesium catalyzed protocol.

Oxidative Addition to Palladium(0) Made Easy through Photoexcited-State Metal Catalysis: Experiment and Computation.

Visible-light induced, palladium catalyzed alkylations of α,ß-unsaturated acids with unactivated alkyl bromides are described. A variety of primary, secondary, and tertiary alkyl bromides are activated by the photoexcited palladium metal catalyst to provide a series of olefins at room temperature under mild reaction conditions. Mechanistic investigations and density functional theory (DFT) studies suggest that a photoinduced inner-sphere mechanism is operative in which a barrierless, single-electron transfer oxidative addition of the alkyl halide to Pd0 is key for the efficient transformation.

Computational Investigation of Carbene-Phosphinidenes: Correlation between 31P Chemical Shifts and Bonding Features to Estimate the π-Backdonation of Carbenes.

Detailed investigations of the electronic structure and bonding scenario in different carbene-phosphinidenes have been presented using state-of-the-art computational methods (BP86/def2-TZVPP//BP86/def2-SVP). We have endeavored to find the correlation of the calculated 31P chemical shifts with different bonding parameters of compounds to access the relative π-acceptor strengths of the carbenes. 31P chemical shifts exhibit a weak correlation with σ-polarizations of Ccarb-P bonds toward phosphorus; however excellent correlations are obtained in the case of π-polarizations of Ccarb-P bonds toward the carbene carbon (Ccarb) and NPA charges on phosphorus atoms. 31P chemical shifts also show excellent correlations with the electron densities and energy densities of Ccarb-P bonds at BCPs, as suggested by QTAIM calculations. Moreover, EDA-NOCV analysis is implemented to gain brief insight into the bonding scenario in this class of compounds. Good correlation exists between the interaction energies between the carbene and PPh fragments and 31P chemical shifts. Additionally, we have investigated the correlations of calculated 31P chemical shifts with different bonding parameters of the corresponding free carbenes. The bonding scenario in different carbene-substituted phosphinidenes is also explored to see how the bonding situation depends on various substituents on phosphinidenes. The other substituted carbene-phosphinidenes show correlations similar to those of carbene-phenylphosphinidenes.

Computational Investigation on the Role of Disilene Substituents Toward N2O Activation.

The effect of substituents in disilene mediated N2O activation was studied at the M06-2X/QZVP//ωB97xD/TZVP level of theory. The relationship between structural diversity and the corresponding reactivity of six disilenes (IA-Ft) in the presence of four different substituents (-NMe2, -Cl, -Me, -SiMe3) is addressed in this investigation. We primarily propose two plausible mechanistic routes: Pathway I featuring disilene → silylene decomposition followed by N2O coordination and Pathway II constituting the N2O attack without Si-Si bond cleavage. Depending on the fashion of N2O approach the latter route was further differentiated into Pathway IIa and Pathway IIb detailing the "end-on" and "side-on" attack to the disilene scaffold. Interestingly, the lone pair containing substituents (-NMe2, -Cl,) facilitates disilene → silylene dissociation; on the contrary it reduces the electrophilicity at Si center in silylene, a feature manifested with higher activation barrier during N2O attack. In the absence of any lone-pair influence from substituents (-Me, -SiMe3), the decomposition of disilenes is considerably endothermic. Therefore, Pathway I appears to be the less preferred route for both types of substituents. In Pathway IIa, the N2O moiety uniformly approaches via O-end to both the silicon centers in disilenes. However, the calculations reveal that Pathway IIa, although not operational for all disilenes, is unlikely to be a viable route due to the predominantly higher transition barrier (ca. 36 kcal/mol). The most feasible route in this current study accompanying moderately low activation barriers (∼19-26 kcal/mol) is Pathway IIb, which involves successive addition of two N2O units proceeding via terminal N, O toward the Si centers and is applicable for all disilenes. The reactivity of substituted disilenes can be estimated in terms of the first activation barrier of N2O attack. Surprisingly, in Pathway IIb, the initial activation barrier and hence the reactivity shows negligible correlation with Si-Si bond strength, indicating toward the versatility of the reaction route.

Exploring the Oxidative-Addition Pathways of Phenyl Chloride in the Presence of PdII Abnormal N-Heterocyclic Carbene Complexes: A DFT Study.

DFT calculations were performed to elucidate the oxidative addition mechanism of the dimeric palladium(II) abnormal N-heterocyclic carbene complex 2 in the presence of phenyl chloride and NaOMe base under the framework of a Suzuki-Miyaura cross-coupling reaction. Pre-catalyst 2 undergoes facile, NaOMe-assisted dissociation, which led to monomeric palladium(II) species 5, 6, and 7, each of them independently capable of initiating oxidative addition reactions with PhCl. Thereafter, three different mechanistic routes, path a, path b, and path c, which originate from the catalytic species 5, 7, and 6, were calculated at M06-L-D3(SMD)/LANL2TZ(f)(Pd)/6-311++G**//M06-L/LANL2DZ(Pd)/6-31+G* level of theory. All studied routes suggested the rather uncommon PdII /PdIV oxidative addition mechanism to be favourable under the ambient reaction conditions. Although the Pd0 /PdII routes are generally facile, the final reductive elimination step from the catalytic complexes were energetically formidable. The PdII /PdIV activation barriers were calculated to be 11.3, 9.0, 26.7 kcal mol-1 (ΔΔ≠ GLS-D3 ) more favourable than the PdII /Pd0 reductive elimination routes for path a, path b, and path c, respectively. Out of all the studied pathways, path a was the most feasible as it comprised of a PdII /PdIV activation barrier of 24.5 kcal mol-1 (ΔGLS-D3 ). To further elucidate the origin of transition-state barriers, EDA calculations were performed for some key saddle points populating the energy profiles.

Estimation of σ-Donation and π-Backdonation of Cyclic Alkyl(amino) Carbene-Containing Compounds.

Herein, we present a general method for a reliable estimation of the extent of π-backdonation (CcAAC←E) of the bonded element (E) to the carbene carbon atom and CcAAC→E σ-donation. The CcAAC←E π-backdonation has a significant effect on the electronic environments of the (15)N nucleus. The estimation of the π-backdonation has been achieved by recording the chemical shift values of the (15)N nuclei via two-dimensional heteronuclear multiple-bond correlation spectroscopy. The chemical shift values of the (15)N nuclei of several cAAC-containing compounds and/or complexes were recorded. The (15)N nuclear magnetic resonance chemical shift values are in the range from -130 to -315 ppm. When the cAAC forms a coordinate σ-bond (CcAAC→E), the chemical shift values of the (15)N nuclei are around -160 ppm. In case the cAAC is bound to a cationic species, the numerical chemical shift value of the (15)N nucleus is downfield-shifted (-130 to -148 ppm). The numerical values of the (15)N nuclei fall in the range from -170 to -200 ppm when σ-donation (CcAAC→E) of cAAC is stronger than CcAAC←E π-backacceptance. The π-backacceptance of cAAC is stronger than σ-donation, when the chemical shift values of the (15)N nuclei are observed below -220 ppm. Electron density and charge transfer between CcAAC and E are quantified using natural bonding orbital analysis and charge decomposition analysis techniques. The experimental results have been correlated with the theoretical calculations. They are in good agreement.

Insertion of Cyclic Alkyl(amino) Carbene into the Si-H Bonds of Hydrochlorosilanes.

Carbenes are known for their ability to abstract HCl from hydrochlorosilanes to form carbene hydrochloride adducts. In contrast, the Si-H bond insertion products RSiCl2(cAACH) (2, 4, 6, and 8) have been formed in the reaction of RSiHCl2 [R = Ar(SiMe3)N (1), Cp* (3), PhC(NtBu)2 (5), Cl (7); Ar = 2,6-iPr2C6H3] with a cyclic alkyl(amino) carbene (cAAC:) irrespective of the steric demand of the R group. The new products have been characterized by various analytical tools including X-ray crystallography, electron ionization mass spectrometry, and NMR spectroscopy. Theoretical investigations have also been performed to understand why cAAC prefers insertion into the Si-H bond rather than the dehydrohalogenation pathway.

Stable radicals from commonly used precursors trichlorosilane and diphenylchlorophosphine.

Intermediate species dichlorosilylene was generated in situ from trichlorosilane and inserted into the P-Cl bond of diphenylchlorophosphine (Ph2P-Cl) to obtain Ph2P-SiCl3 (1). Monodechlorination of 1 by cyclic alkyl(amino) carbenes (cAACs)/KC8 in THF at low temperature led to the formation of stable radicals Ph2P-Si(cAAC·)Cl2 (2a,b). Compounds 2a,b were characterized by X-ray single crystal diffraction, mass spectrometry and studied by cyclic voltammetry and theoretical calculations. Radical properties of 2 are confirmed by EPR measurements that suggest the radical electron in 2 couples with (14)N (I = 1), (35/37)Cl (I = 3/2), and (31)P (I = 1/2) nuclei leading to multiple hyperfine lines. Hyperfine coupling parameters computed from DFT calculations are in good agreement with those of experimental values. Electronic distributions obtained from the theoretical calculations suggest that the radical electron mostly resides on the carbene C of 2.

Regio- and Diastereoselective and Enantiospecific Metal-Free C(sp(3) )-H Arylation: Facile Access to Optically Active 5-Aryl 2,5-Disubstituted Pyrrolidines.

Optically active 5-aryl 2,5-disubstituted pyrrolidines are the principal structural moiety of many bioactive compounds including natural products and catalysts for asymmetric synthesis. A highly regio- and diastereoselective and enantiospecific method for direct C-H arylation of aliphatic amine has been developed. Structurally diverse enantiopure arylated pyrrolidines were synthesized from commercially available starting materials, through a single-step three-component reaction under metal- and oxidant-free conditions. Furthermore, the complex analogous structure of CCK antagonist RP 66803 and angiotensin-converting enzyme inhibitors was easily constructed using the synthesized arylated pyrrolidine derivative. Detailed theoretical calculations (M06-2X/TZVPP/SMD//M06-2X/6-31+G(d,p) level) were also carried to investigate the mechanism and high level of stereocontrol involved in this direct sp(3) C-H arylation reaction. Preference for a given regio- and stereoselectivity in the arylated product can be explained through elucidation of the mechanism for dehydration, generating azomethine ylide, and for the final re-aromatization step. The calculated energies reveals that the re-aromatization step is essentially rate determining, accompanying an activation barrier of Δ(≠) G=25.6 kcal mol(-1) .